Aspirin inhibition of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced lesions of the urinary bladder correlated with inhibition of metabolism by bladder prostaglandin endoperoxide synthetase.
The effects of aspirin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) -induced urinary bladder lesions, endogenous bladder prostaglandin E2 synthesis, and the metabolism of FANFT by bladder epithelial microsomes were examined. Rats were fed 0.5% aspirin and/or a diet containing 0.1% or 0.2% FANFT. Bladder lesions were observed with light and scanning electron microscopy, and the prostaglandin E2 content of rat bladder was measured by radioimmunoassay. Metabolism of FANFT was measured by decreased absorbance at 400 nm. Aspirin inhibited the appearance of hyperplastic lesions induced by feeding 0.1% or 0.2% FANFT for 6 or 12 weeks. Aspirin reduced bladder prostaglandin E2 content at 1, 2, 6, and 13 weeks compared to corresponding control values. Rat and rabbit microsomal metabolism of FANFT were dependent upon specific fatty acid substrate and prevented by specific inhibitors (including aspirin) of prostaglandin endoperoxide synthetase. Other inhibitor and substrate specificity studies suggest that FANFT was not metabolized by xanthine oxidase, lipoxygenase, lipid peroxidation, or mixed-function oxidases. These results suggest that the metabolism of FANFT by prostaglandin endoperoxide synthetase may be involved in the metabolic activation of FANFT necessary for the induction of bladder cancer in rats.
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001711:Biotransformation; D016861:Cyclooxygenase Inhibitors; D005200:FANFT / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006965:Hyperplasia / Q000139:chemically induced; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced; D011458:Prostaglandins E / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D013844:Thiazoles / Q000037:antagonists & inhibitors*; D001743:Urinary Bladder / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D016861:Cyclooxygenase Inhibitors; D011458:Prostaglandins E; D013844:Thiazoles; D005200:FANFT; D001241:Aspirin